Contrast-enhanced breast magnetic resonance imaging (MRI) is a clinically useful tool for breast cancer screening in high-risk women and the diagnosis, staging, and clinical management of breast cancer patients, and may also have utility in the determination of breast cancer risk. Normal breast fibroglandular tissue (FGT), which appears white on mammography (i.e. mammographic density (MD)), is a well-established risk factor for breast cancer. FGT is also visible on breast MRI (MRI-FGT) and enhances (becomes brighter) to varying extents after administration of MRI-contrast medium. Background parenchymal enhancement (MRI-BPE) is a measure of the volume and intensity of this enhancement. In a study of 39 breast cancer cases and 78 cancer- free controls undergoing breast screening with MRI, MRI-BPE was strongly associated with breast cancer risk; women in the highest MRI-BPE category had a 7.5-fold higher risk of breast cancer compared with those in the lowest MRI-BPE groups. MRI-BPE only weakly correlated with MRI-FGT, which is strongly correlated with MD, indicating that MRI-BPE may be an independent marker of breast cancer risk. We propose to confirm these findings by conducting a multi-center, hospital-based, case-control study examining MRI-BPE and MRI-FGT as markers of breast cancer risk. Across three centers we will recruit, interview, and collect medical records and pre-treatment MRIs and mammograms from 1,110 women with invasive breast cancer (cases) and 1,110 high- risk women who are cancer-free and are undergoing MRI breast cancer screening (controls). Clinical data and tumor characteristics (for cases) will be abstracted through electronic medical record review. MRI-BPE and MRI-FGT will be scored by a single reader using standard clinical measures and mammographic percent density (MPD) using Cumulus. We also propose to measure both MRI-BPE and MRI-FGT using a new fully automated method. Our hypothesis is that while MRI-FGT and MPD measure the amount of FGT, MRI-BPE is a marker of breast tissue activity, contributing to breast cancer risk independently of the amount of FGT present. Our Primary Aim is to examine the relationship between MRI-BPE and MRI-FGT measured by Breast Imaging-Reporting and Data System (BI-RADS) categories, and breast cancer risk. Our Secondary Aims are: 1) to determine whether the inclusion of MRI-BPE improves breast cancer risk assessment over that achieved by MPD alone; and 2) to examine the association between MRI-BPE and MRI-FGT, measured on a continuous scale by a novel automated computerized method, and breast cancer risk. In the long-run MRI-BPE could greatly improve the accuracy of breast cancer risk prediction among high-risk women undergoing breast MRI screening by identifying a subgroup of women who would benefit the most from heightened screening and preventive measures and possibly a subgroup of women at lower risk who may benefit from less intensive screening. The automated quantitative measures of MRI-BPE and MRI-FGT would greatly facilitate the incorporation of these measures into widespread clinical and research practice.